The team of Sylvain Latour is internationally recognized in the field of primary immunodeficiencies. The team has developed over the years a strong expertise in the identification and characterization of inherited monogenic immune deficiencies associated with a high susceptibility to Epstein Barr virus (EBV) infection and EBV-driven B cell lymphomas, which are mostly childhood diseases. Notably, studies of these primary immune deficiencies allowed the discovery of novel key factors/mechanisms involved the immune response against EBV, and more generally in the immuno-surveillance of lymphomas. Notably, they showed that T-cell expansion is a key step of immune response to EBV infection. In particular, they recently identified two co-stimulatory receptors of the TNF receptor family, CD27 and TNFRSF9 (also known as CD137/4-1BB) and their ligands (CD70 and TNFSF9) as critical pathways for immunity to EBV. The team has recently developed a strong interested in the “atypical” EBV infections when EBV infects and persists in T, NK and smooth muscle cells leading to T/NK lymphomas and smooth muscle tumors (SMT).

The team will mainly contribute to the WP1 and will collaborate closely with the teams of V. Asnafi and F. de Vathaire to identify new genetic predisposition factors to childhood hematopoeitic malignancies involved in immunity and lymphomagenesis through analyses of patients. In these studies, association and interplay between somatic and germinal mutations as well as polygenic mode of predisposition will be considered (for new genes and genes already known to be associated with a high risk of lymphoma). Those analyses will include identification of rare and less rare variants (SNPs), identification/calculation of polygenic and pathway-specific genetic risk scores. Depending of their function, new genes and pathways could be analyzed in collaboration with teams of WP2 and WP3.

The team has initiated a collection of whole exome data from pediatric patients (with relatives) with lymphoma (project PID-Ls and EuroNet Hodgkin Lymphoma group) that are recruited in collaboration with the Lymphoma committee of the SFCE directed by T. Leblanc (project PID-Ls and EuroNet Hodgkin Lymphoma group), the Centre d’Etude des Déficits Immunitaires (CEDI directed by Capucine Picard) and some worldwide collaborations of team.

The specific expertise and skills of the team are:
     ● Recruitment of patients with lymphoma
     ● WES sequencing, targeting exon sequencing
     ● Analysis of WES data
     ● Identification of rare variants
     ● Functional validation of identified variants
     ● Analysis of T lymphocytes responses and signaling
     ● CRISPR-Cas9 based technologies in cell lines and mice models including correction of mutations from cells of patients
     ● ShRNA based approaches in lymphocytes
     ● Development and analysis of mice models mimicking identified variations found in patients